2019 Fiscal Year Final Research Report
Mechanical properties of microtubule motors and the mechanisms of mitosis
| Project/Area Number |
16H06166
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biophysics
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| Research Institution | National Institute of Genetics |
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Principal Investigator |
Shimamoto Yuta 国立遺伝学研究所, 遺伝メカニズム研究系, 准教授 (80409656)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 有糸分裂 / 微小管 / 分子モーター / 染色体分配 / 紡錘体 / メカニクス |
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| Outline of Final Research Achievements |
We used a combination of biophysical force measurement, high-resolution imaging, biochemical perturbation, and materials science methods to elucidate the physical and molecular basis underlying the assembly of the metaphase spindle - the eukaryotic chromosome segregation machinery. We find that the spindle has a substantial mechanical heterogenity along the axis to which chromosomes are segregated, and the heterogeneity is linked to two key microtubule-based motors, kinesin-5 and dynein (Takagi et al., Dev Cell 2019). Our data propose how the spindle exerts relevant forces for chromosome segregation while adapting to perturbations for error-free cell division. We have also developed a method to prepare a frozen stock of Xenopus egg extracts with retained spindle assembly activity (Takagi et al., Mol Biol Cell 2019). Together, our study should help advance our understanding of spindle micromechanics in a variety of cellular contexts, such as those during embryonic development.
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| Free Research Field |
生物物理学
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| Academic Significance and Societal Importance of the Research Achievements |
有糸分裂・減数分裂期における母細胞から娘細胞への遺伝情報の継承は、紡錘体と呼ばれるミクロンサイズの生体装置によって行われる。紡錘体に生じる欠陥はガンや不妊症と密接に関連する。本研究は、紡錘体が細胞内で正確に形成し機能を果たすしくみの一端を、その主骨格である微小管と、微小管を組み上げるモータータンパク質に着眼することで明らかにしたものである。本研究の成果は、紡錘体が自らのサイズを柔軟に調節しながら染色体を安定に分配するための物理的基礎と分子基盤を示唆するものであり、この細胞装置の動作原理の定量的理解に根ざした新たな疾患治療戦略の創出が期待される。
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